In a non‑immunosuppressed adult, how can I differentiate bacterial from viral infections and determine whether antibiotics are indicated?

Differentiating Bacterial from Viral Infections in Non-Immunosuppressed Adults

Use a combination of clinical trajectory, specific symptom patterns, and procalcitonin (PCT) levels to distinguish bacterial from viral infections—with PCT <0.25 ng/mL strongly suggesting viral etiology and PCT >0.5 ng/mL indicating bacterial infection—but never delay empiric antibiotics in severely ill patients while awaiting test results. 1, 2

Clinical Features That Distinguish Bacterial from Viral Infections

Respiratory Tract Infections

For upper respiratory infections, look for three specific patterns that indicate bacterial rather than viral etiology:

• Persistent symptoms without improvement for at least 10 days suggest bacterial sinusitis rather than viral upper respiratory infection 1
• Severe symptoms with high fever (>38°C) and purulent nasal discharge for at least 3 consecutive days indicate bacterial infection 1
• "Double-worsening" pattern—where symptoms initially improve then worsen again within 10 days—strongly suggests bacterial superinfection 1

Lower Respiratory Infections (Pneumonia vs Viral Bronchitis)

Distinguish pneumonia from viral bronchitis using this approach:

• Vital sign abnormalities are prominent in pneumonia: heart rate >100 beats/min, respiratory rate >24 breaths/min, temperature >38°C, blood pressure <90/60 1
• Upper respiratory symptoms (rhinorrhea, sore throat, nasal congestion) favor viral infection over bacterial pneumonia 1
• C-reactive protein (CRP) <20 mg/L makes pneumonia unlikely**, while **CRP >100 mg/L makes it likely (area under ROC curve 0.80) 1

Pharyngitis

Use the modified Centor criteria to determine who needs testing for bacterial (streptococcal) pharyngitis:

• Patients meeting fewer than 3 Centor criteria (fever by history, tonsillar exudates, tender anterior cervical adenopathy, absence of cough) do not need testing 3
• Presence of cough, nasal congestion, conjunctivitis, hoarseness, diarrhea, or oropharyngeal ulcers/vesicles strongly suggests viral etiology and testing should not be performed 3

Chronic Bronchitis Exacerbations

For chronic obstructive bronchitis, use the Anthonisen triad—antibiotics are indicated only when at least 2 of 3 criteria are present:

• Increased volume of expectoration 3
• Increased purulence of expectoration 3
• Increased dyspnea 3

Fever alone does not distinguish bacterial from viral causes, but persistence >3 days suggests bacterial infection 3

Laboratory Testing Strategy

Procalcitonin (PCT) - The Most Useful Single Biomarker

PCT is the most reliable biomarker for distinguishing bacterial from viral infections:

• PCT <0.25 ng/mL has high negative predictive value for ruling out bacterial infections 2, 4
• PCT >0.5 ng/mL strongly suggests bacterial infection 2, 4
• Serial PCT measurements are more valuable than single measurements, especially in critically ill patients 2

Critical caveat: PCT has sensitivity of only 38-91% for bacterial infections, so low PCT cannot definitively exclude infection 4

Complete Blood Count (CBC) - Limited Utility

CBC patterns alone should never guide antibiotic decisions:

• No single CBC parameter reliably distinguishes bacterial from viral infections 2
• Neutrophil predominance suggests bacterial infection while lymphocytic predominance favors viral etiology, but exceptions are extremely common 2
• The distribution of WBC and neutrophil counts is too wide within bacterial and viral groups to identify reliable cutoff points 2

Integrated Biomarker Approach

Combine PCT with CRP and clinical trajectory for optimal accuracy:

• Obtain CBC with differential, PCT, and CRP at presentation 2
• Assess clinical trajectory: duration of symptoms, fever pattern, and progression versus improvement 2
• If PCT <0.25 ng/mL, bacterial infection is unlikely and antibiotics may be withheld 2
• If PCT >0.5 ng/mL with neutrophil predominance, bacterial infection is likely and antibiotics should be initiated 2

Advanced Diagnostics

For hospitalized patients with pneumonia:

• Multiplex PCR for respiratory pathogens reduces antibiotic use by 22-32% when viral pathogen is detected 2
• Blood cultures (two sets, 60 mL total from different anatomical sites) should be obtained before starting antibiotics 1
• Rapid antigen detection for influenza provides results in 15-30 minutes but has limited sensitivity (50-70% in adults), so negative results do not exclude viral infection 1

When Antibiotics Are NOT Indicated

Do not prescribe antibiotics in these situations:

• Acute bronchitis without suspected pneumonia—antibiotics show no benefit and increase adverse events 3
• Pharyngitis with <3 Centor criteria or presence of viral symptoms (cough, rhinorrhea, conjunctivitis) 3
• Simple chronic bronchitis exacerbation even with fever present 3
• Viral upper respiratory infection without the three bacterial patterns described above 1

When Antibiotics ARE Indicated

Initiate antibiotics immediately in these scenarios:

• Chronic obstructive bronchitis with chronic respiratory insufficiency (dyspnea at rest, FEV1 <35%, hypoxemia at rest) during any exacerbation 3
• Bacterial pneumonia based on vital signs, CRP >100 mg/L, and clinical presentation 1
• Pharyngitis with ≥3 Centor criteria AND positive rapid strep test or culture 3
• Bacterial sinusitis meeting one of the three specific patterns (persistent >10 days, severe symptoms ≥3 days, or double-worsening) 1

Critical Pitfalls to Avoid

Common diagnostic errors that lead to inappropriate antibiotic use:

• Misdiagnosing viral infections as bacterial is the most common pitfall, leading to unnecessary antibiotic use and contributing to resistance 1, 2
• Using fever alone to diagnose bacterial infection—fever does not reliably distinguish bacterial from viral causes 3
• Relying on CBC patterns alone without integrating PCT and clinical trajectory 2
• Delaying empiric antibiotics in severely ill patients while awaiting PCT results—in suspected sepsis or septic shock, immediate broad-spectrum antibiotics are mandatory regardless of biomarker values 4

Special Populations Requiring Careful Monitoring

These patients are at higher risk for complications and bacterial superinfection:

• Patients with COPD, diabetes, or heart failure require careful monitoring 1, 2
• Approximately 10% of immunocompetent adults hospitalized with community-acquired pneumonia have viral infection, and viral-bacterial coinfection occurs in up to one-third of cases 1
• Streptococcus pneumoniae is the most common bacterial superinfection following viral respiratory infection 1